1. Field of the Invention
The present invention concerns the therapeutic use of certain anti-CD22 monoclonal antibodies with unique physiologic properties. More specifically, the invention concerns methods of treating B-cell malignancies, such as lymphomas and leukemias, and autoimmune diseases with blocking anti-CD22 antibodies having unique pro-apoptotic properties.
2. Description of the Related Art
CD22 is a membrane glycophosphoprotein found on nearly all B lymphocytes and most B-cell lymphomas. Cross-linking CD22 triggers CD22 tyrosine phosphorylation, and assembles a complex of effector proteins that activate the stress-activated protein kinase (SAPK) pathway. CD22 cross-linking provides a potent costimulatory signal in primary B-cells and pro-apoptotic signal in neoplastic B-cells. Structurally, CD22 is a member of the “sialoadhesin” subclass of the immunoglobulin (Ig) gene superfamily, having seven extracellular Ig domains with a single amino-terminal V-set Ig domain and six C-2 set Ig domains. Wilson et al, J. Exp. Med. 173:137-146 (1991); Engel et al., J. Exp. Med. 181: 1581-1586 (1995): and Torres et al., J. Immunol. 149:2641-2649 (1992). It has been shown that CD22 is a critical lymphocye-specific signal transduction molecule which negatively and positively regulates B lymphocyte antigen receptor (BCR) signaling by recruiting signaling effector molecules to physiologically pertinent sites. Tedder et al., Annu. Rev. Immunol. 15:481-504 (1997); Sato et al., Immunology 10:287-297 (1998).
Anti-CD22 antibodies have been described, for example in U.S. Pat. Nos. 5,484,892; 6,183,744; 6,187,287; 6,254,868, and in Tuscano et al., Blood 94(4):1382-92 (1999). The use of monoclonal antibodies, including anti-CD22 antibodies, in the treatment of non-Hodgkin's lymphoma is reviewed, for example, by Renner et al., Leukemia 11(Suppl. 2):S55-9 (1997). A. humanized anti-CD22 antibody, LymphoCide™ (empatuzumab, Immunomedics, Inc.) is in Phase III clinical trials for the treatment of indolent and aggressive forms of non-Hodgkin's lymphomas. An yttrium-90-labeled version of this antibody is currently in Phase I clinical trials for the same indication.
Despite recent advances in cancer therapy, B-cell malignancies, such as the B-cell subtype of non-Hodgkin's lymphoma, and chronic lymphocytic leukemia, are major contributors of cancer-related deaths. Accordingly, there is a great need for further, improved therapeutic regimens for the treatment of B-cell malignancies. Autoimmune diseases as a whole cause significant morbidity and disability. Based on incidence data collected from 1965 to 1995, it has been estimated that approximately 1,186,015 persons will develop a new autoimmune disease over the next 5 years, Jacobsen et al. (Clin. Immunol. Immunopathol. 84:223 (1997)) evaluated over 130 published studies and estimated that in 1996, 8.5 million people in the United States (3.2% of the population) had at least one of the 24 autoimmune diseases examined in these studies. Considering the major impact of autoimmune diseases on public health, effective and safe treatments are needed to address the burden of these disorders. Thus, there is a need in the art for improved reagents and methods for treating autoimmune disease.